DESCRIPTION: (Applicant's Abstract) Histatins are small cationic peptides present in human saliva which exhibit potent antifungal properties and contribute to the non-immune (innate) protection of the oral mucosa. Structural, embryological, and functional similarities shared by oral and ocular mucosal membranes suggest the development of common antimicrobial defense strategies. Preliminary studies in this laboratory have, for the first time, demonstrated the presence of histatin in the both the conjunctiva and lacrimal gland. Diverse populations including the immunocompromised, diabetic and elderly patients are particularly susceptible to fungal infection of mucosal surfaces. These infections are often resistant to standard therapies and, in the case of the ocular surface, can lead to permanent loss of vision. Enhancement of innate mucosal defense capabilities is therefore a potentially effective strategy for controlling and combating such infections. We propose to identify and quantify the-histatin in tear film by mass spectroscopy. In situ hybridization of ocular tissues will allow for-the localization of histatin transcripts. Cytokine and microbial challenge to human conjunctival cells and subsequent quantification of histatin transcripts by competitive PCR will identify the regulatory mechanisms of histatin transcription. Lastly, we will quantify salivary and lacrimal histatin from Sjogren's patients in order to determine the effect of autoimmune destruction of glandular tissue on the abundance of this antifungal peptide. These studies will contribute to the development of innovative therapeutic strategies to combat fungal infection in ocular tissue.